Since 1982, investigators from the Radiation Epidemiology Branch (REB), NCI and the University of Minnesota have been following a large, mostly female (73%), cohort of U.S. radiologic technologists for the purpose of evaluating and quantifying carcinogenic risks of protracted, low-dose, fractionated radiation exposures. The cohort offers important advantages over other occupational radiation cohorts, including validated cancer incidence outcomes, comprehensive covariate data, and a large female membership, which affords a rare opportunity to study low-dose effects on the breast and thyroid in women. Recent analyses using relatively crude exposure indices revealed significantly elevated risks for certain cancers (e.g., breast, leukemia, non-melanoma skin, melanoma) associated with working in the earlier calendar years, when occupational radiation exposures were likely high. Estimates of annual radiation doses for individual radiologic technologists are now being developed in collaboration with health physicists and industrial hygienists from the National Institute for Occupational Safety and Health, as well as records from a commercial dosimetry company, Landauer, Inc. Detailed statistical modeling and review of the literature on historical exposures is nearing completion, and preliminary dose estimates will be available in late 2001. More than 1,000 biospecimen samples have been collected from primarily breast cancer cases. Analyses are underway to evaluate candidate breast cancer susceptibility genes and we will soon begin polymorphic variant analyses of multiple DNA repair genes. A cohort of 20,000 Mayak nuclear facility workers (in the former Soviet Union)is being studied because they comprise a unique occupational group for protracted exposure to external radiation at high doses, and exposure to plutonium and strontium. Mortality analyses of the Mayak workers demonstrate that internal exposure to plutonium results in excess risk of bone and liver cancer, with higher risks for females than males. Dosimetry reconstruction is underway to evaluate the shape of the dose-response function. In addition, initial analyses evaluating the effects of external radiation exposure, showed dose-response relationships for leukemia and all solid cancers. Several studies of Chornobyl clean-up workers are currently underway. Cancer incidence through 1998 is being evaluated in three cohorts, comprising 17,000 clean-up workers, from Estonia, Latvia, and Lithuania who were sent to Chornobyl (Ukraine) following the reactor accident in 1986. Cohort members are interviewed to elicit other risk factor information. In addition, with support from DOE and NRC, NCI is conducting a "nested" study of leukemia and other hematologic disease among the Chornobyl clean-up workers in Ukraine. A cancer incidence study is planned to determine whether female flight attendants are at increased risk of breast or other cancers due to cosmic radiation exposure. A biodosimetry study to assess cosmic radiation exposure will compare the induction and persistence of chromosome aberrations by fluorescence in situ hybridization (FISH) among 90 pilots and 50 university faculty with minimal flying experience.